Abstract
The enveloped alphavirus Semliki Forest virus (SFV) infects cells via a low pH-triggered membrane fusion reaction mediated by the E1 protein. E1's fusion activity is regulated by its heterodimeric interaction with a companion membrane protein E2. Mature E2 protein is generated by furin processing of the precursor p62. Processing destabilizes the heterodimer, allowing dissociation at acidic pH, E1 conformational changes, and membrane fusion. We used a furin-deficient cell line, FD11, to select for SFV mutants that show increased growth in the absence of p62 processing. We isolated and characterized 7 such pci mutants (p62 cleavage independent), which retained the parental furin cleavage site but showed significant increases in their ability to carry out membrane fusion in the p62 form. Sequence analysis of the pci mutants identified mutations primarily on the E2 protein, and suggested sites important in the interaction of p62 with E1 and the regulation of fusion.
Original language | English (US) |
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Pages (from-to) | 287-296 |
Number of pages | 10 |
Journal | Virology |
Volume | 327 |
Issue number | 2 |
DOIs | |
State | Published - Oct 1 2004 |
Keywords
- Alphavirus
- Endocytosis
- Furin
- Membrane fusion
- Protein processing
- Semliki Forest virus
- Virus entry
ASJC Scopus subject areas
- Virology